Skin and So) Tissue Infec1ons: MRSA and Beyond

Overview Skin and So) Tissue Infec1ons: MRSA and Beyond Catherine Liu, M.D. Assistant Clinical Professor Division of Infec1ous Diseases University of California, San Francisco 2011 IDSA MRSA Treatment Guidelines Management of skin and so) 1ssue infec1ons (SSTI) Abscesses Celluli1s (purulent vs. non- purulent) Complicated SSTI Animal Bites Necro1zing fascii1s Other SSTI Case 1 What is the appropriate management of this pa1ent? 20 y/o M presents with 3 days of an enlarging, painful lesion on his L arm that he avributes to a spider bite T 36.9 BP 118/70 P 82 A. Incision and drainage alone B. Incision and drainage plus oral an1- MRSA an1microbial agent C. Oral an1- MRSA an1microbial agent 1

Abscesses Incision and drainage is the primary treatment (AII). For simple abscesses or boils, I&D alone likely adequate Do an1bio1cs provide addi1onal benefit? Clinical cure p=.25 p=.12 cephalexin TMP-SMX TMP-SMX p=.52 An1bio1c therapy is recommended for abscesses associated with: Severe, extensive disease, rapidly progressive with associated celluli1s or sep1c phlebi1s Signs & sx of systemic illness Associated comorbidi1es, immunosuppressed Extremes of age Difficult to drain area (e.g. face, hand, genitalia) Failure of prior I&D (AIII) 1 Rajendran AAC 2007; 2 Duong Ann Emerg Med 2009; 3 Schmitz G Ann Emerg Med 2010 Liu CID 2011; 52: 285-322 Microbiology of Purulent SSTIs: ER Pa1ents Purulent Celluli1s viridans strep; 2% B- hemoly3c strep; 2% coag neg staph; 6% MSSA 16% other/ unknown, 15% 2004 2008 MRSA 59% Celluli1s associated with purulent drainage or exudate without a drainable abscess Empiric Rx for CA- MRSA is recommended (AII). Empiric Rx for β- hemoly1c strep unlikely needed (AII). Dura1on of therapy: 5-10 days, individualize based on clinical response Moran NEJM 2006; Talan CID 2011 Liu CID 2011; 52: 285-322 2

Outpa1ent purulent celluli1s: Empiric Rx for CA- MRSA Case 2 TMP/ SMX 1-2 DS tab BID Doxycycline, Minocycline 100 mg BID Clindamycin 300-450 TID Linezolid 600 mg BID MRSA MSSA β- hemoly3c strep Comments + + - Low rates of resistance + + - Low rates of resistance +/- ( resistance) + + C. diff risk + + + Most expensive op1on 28 year old woman with erythema of her le) foot x 48 hours. No purulent drainage, exudate or abscess. T 37.0 BP 132/70 P 78 Eells SJ et al Epidemiology and Infec1on 2010 What is the appropriate management of this pa1ent? A. Clindamycin 300 mg PO 1d B. Cephalexin 500 mg QID, monitor clinically with addi1on of TMP/SMX if no response C. Cephalexin 500 mg QID and TMP/ SMX 2 DS tab PO bid Nonpurulent Celluli1s: β- hemoly1c strep vs. staph? Empiric Rx for β- hemoly1c strep recommended (AII) Prospec1ve study 1, 248 hospitalized pts 73% due to β- hemoly3c strep 27% with no iden1fied cause. Overall 96% response rate to β- lactam an1bio1c (cefazolin, oxacillin, cephalexin, dicloxacillin). Retrospec1ve study 2 treatment failures with TMP- SMX vs. β- lactam or clindamycin Consider coverage for MRSA if: Penetra1ng trauma, IVDU Evidence of MRSA infec1on elsewhere Failure to respond to β- lactam Systemic signs and symptoms 1 Jeng et al Medicine 2010; 2 EllioV et al Pediatrics 2009; Liu CID 2011; 52: 285-322 3

Cephalexin vs. Cephalexin + TMP- SMX in pa1ents with Uncomplicated Celluli1s Outpa1ent nonpurulent celluli1s: Empiric Rx for β- hemoly1c streptococci, +/- MRSA N=146 MRSA MSSA β- hemoly3c strep Cephalexin 500 mg QID Dicloxacillin 500 mg QID Clindamycin 300-450 mg TID - + + - + + +/- ( resistance) + + Linezolid 600 mg BID + + + Pallin CID 2013 322 hospitalized pa1ents with celluli1s, abscess, complicated SSTI 97% of cases had S. aureus or Streptococcus spp. 74% S. aureus or Streptococcus ONLY Microbiology of SSTI: Hospitalized Pa1ents Enterococci 3% Implementa1on of a clinical prac1ce guideline for inpa1ent celluli1s and abscess July 2009-2010: Empiric Rx: IV vancomycin, then tailor to culture, step- down to PO therapy for 5-7 days Specifically discouraged: Gram nega1ve and an1- anaerobic agents ESR CRP Plain films, CT, MRI Developed electronic admission order set Educa1onal campaign for faculty and housestaff peer champions from 5 departments (ER, adult urgent care, internal medicine, general surgery, orthopedic surgery) Audit/ feedback Jenkins CID 2010; 51: 895-903 Jenkins Arch Intern Med 2011; 171: 1072-9 4

An1bio1c U1liza1on Post- Interven1on * Other Outcomes Median dura1on of Rx (13 vs. 10d, p<.001) * No differences in clinical outcomes Clinical failure (7.7% vs. 7.4%, p=ns) Recurrent infec1on * * *p<.05 Rehospitaliza1on due to SSTI Length of hospital stay Jenkins Arch Intern Med 2011; 171: 1072-9 Jenkins Arch Intern Med 2011; 171: 1072-9 Complicated SSTI Surgical debridement & empiric Rx for MRSA pending cx An1bio1c Adult Evidence Grade Vancomycin 15-20 mg/kg IV Q8-12 AI Linezolid 600 mg PO/ IV BID AI Daptomycin 4 mg/kg IV QD AI Telavancin 10 mg/kg IV QD AI Clindamycin 600 mg PO/IV Q8 AIII Ce)aroline 600 mg IV Q12 FDA approved a)er guidelines Tigecycline 100 mg IV x 1, then 50 IV Q12 Consider alternate agent as associated with mortality Liu CID 2011; 52: 285-322 What about Decoloniza1on for Preven1on of Recurrent SSTI? Mupirocin containing regimens (+/- chlorhexidine, bleach) reduce S. aureus coloniza1on S1ll no clear data that shows decoloniza1on prevents recurrent SSTI Open- label RCT of 300 pts with SSTI and S. aureus coloniza1on No difference in recurrent SSTI with hygiene educa1on alone vs mupirocin + hygiene educ. vs mupirocin/ CHG + hygiene educ. vs mupirocin/ bleach + hygiene educ. Fritz ICHE 2011; 32:872-80 5

Household vs. Individual Decoloniza1on? Open- label RCT children with community- onset SSTI and S. aureus coloniza1on (nares, axilla, inguinal) 2 Index case vs. household decoloniza1on (mupirocin + CHG baths x 5d) All received hygiene educa1on: Avoid sharing personal hygiene items Use liquid pump or pour soaps and lo1ons (vs. bar soaps and lo1on jars) Launder towels and washcloths a)er each use Launder bed linens once weekly No difference in rate of eradica1on of S. aureus carriage. @ 1 month: 50% vs. 51% (p = 1.0) @ 12 months: 54% vs. 66% (p=.28) Liu CID 2011; 52: 285-322 Fritz CID 2012; 54:743-51 Recurrent SSTI among Cases and Household Contacts p=.02 p=.008 p=.02 Summary: empiric management of SSTIs Uncomplicated I&D Purulent (MRSA) Consider addi1on of an1- MRSA an1bio1c in select situa1ons 1 Non- purulent (β- hemoly1c strep) Cephalexin 500 QID Dicloxacillin 500 QID Consider MRSA ac1ve agent in select situa1ons 2 p=.12 Fritz CID 2012; 54: 743-51 Complicated I&D plus vancomycin (or alterna1ve),no gram neg in most cases 3 Vancomycin (or alterna1ve), no gram neg in most cases 3 1. Systemic illness, purulent celluli1s/wound infec1on, comorbidi1es, extremes of age, abscess difficult to drain or face/hand, sep1c phlebi1s, lack of response of to I&D alone. PO an1bio1c : TMP- SMX 1-2 DS BID, Clindamycin 300 mg TID, Doxycycline 100 PO BID 2. Penetra1ng trauma (e.g. IVDU), evidence of MRSA elsewhere, failure to respond to β- lactams, systemic illness 3. Except: cri1cally ill pts with serious SSTI (nec fasc), perirectal/ periorbital infec1ons, decubitus ulcer infec1ons, severe diabe1c foot infec1ons, animal bites, water- exposure 6

Case 3 21 yo M is tossing a ball in Golden Gate Park with a friend. As he goes a)er the ball, he passes close to a dog that was res1ng in the shade with his owner. The dog jumps up and bites him on the leg inflic1ng several deep puncture wounds on the calf. In addi1on to wound care, what is the appropriate management of this pa1ent? A. An1bio1c prophylaxis with clindamycin B. An1bio1c prophylaxis with amoxicillin/ clavulanate C. Administer rabies immunoglobulin and rabies vaccine for post- exposure prophylaxis D. A and C E. B and C Microbiology of Animal Bites: What s in your mouth and on your skin Average 5 organisms (range 0-16) per wound Dogs Cats Pasturella sp 50% 75% Streptococcus sp. 46% 46% Staphylococcus aureus 20% 4% Anaerobes mixed w/ aerobes 48% 63% Anaerobes alone 1% 0% Talan NEJM 1999 An1bio1c Coverage for Pasteurella What you want to use but won t work cephalexin dicloxacillin clindamycin What works Amoxicillin/ penicillin doxycycline fluoroquinolones 7

Animal bites Rabies what type of bites are high risk? Empiric treatment regimens Amoxicillin/clavulanic acid +/- an1- MRSA Pen allergy: cipro + clindamycin or moxifloxacin Prophylaxis? Moderate- severe bites or on face/hands Immunocompromised (splenectomized) Cat bites (50% infec1on risk) Animal Type Dog, cats, ferrets Skunk, raccoons, foxes, bats Livestock, small rodents, rabbits, large rodents Evalua1on and disposure of animal Suspected/confirmed rabid Healthy Animal lost Regarded as rabid unless proven nega1ve by lab test Consider individually Post- exposure prophylaxis Prophylaxis 10 days observa1on/test Contact DPH Immediate prophylaxis Almost never require prophylaxis http://www.cdc.gov/mmwr/pdf/rr/rr57e507.pdf 39 yo M IVDU with 1 day h/o L leg pain and erythema, worsening pain and swelling x 24 hours T 39.2 P120 BP96/60 R22 98%RA Case 3 What would your empiric therapy be in this case? A. Admit, IV vancomycin and piperacillin- tazobactam B. Call surgery, IV vancomycin and clindamycin C. Call surgery, IV vancomycin, piperacillin- tazobactam, clindamycin 18>40<425, le) shi) 8

Necro1zing skin and so) infec1ons Monomicrobial (Group A strep > S. aureus, Clostridia, gram neg rare) Polymicrobial (gram +, gram -, anaerobes) associated w/ abdominal surgery, decub ulcers, IVDU, spread from GU tract Risk Factors for Necro3zing SSTI IVDU Diabetes Obesity Chronic immunosuppression O)en no precipita1ng factor Anaya DA. Clin Infect Dis. 2007 Clinical Presenta1on Nonspecific complaints: pain, GI (N/V/D), influenza- like symptoms Physical exam difficult to dis1nguish from celluli1s, some1mes only mild local erythema pain out of propor3on Missed Dx of Necro1zing Fascii1s Ini3al Diagnoses by PCP/ ER No. Musculoskeletal Pain 6 (40%) Influenza 3 (20%) Gastroenteri1s 2 (13%) Hemorrhoids 1 (6%) Gout 1 (6%) 1 burn 1 (6%) Varicella 1 (6%) Bisno CID 2000 Wong CH Crit Care Med 2004 % of pa3ents 100 90 80 70 60 50 40 30 20 10 0 Necro1zing so) 1ssue infec1ons: physical findings on admission Tenderness Erythema Warmth Bullae Indura1on Fluctuance n=89; 14% dx with nec fasc on admit Late findings Crepitus Necrosis Sensory/ motor deficits Hypotension Fever Tachycardia Wong CH. Jour of Bone and Joint Surg. 2003 9

Necro1zing so) 1ssue infec1ons: radiographic techniques Why is Early Diagnosis So Important? Plain films Low sensi1vity Helpful if gas present CT and ultrasound May iden1fy other Dx (abscess) MRI Enhanced sensi1vity, low specificity Dufel S, Martino M. J Fam Pract. 2006;55(5):396. Wong CH. J of Bone and Joint Surg. 2003 Summary: Management of necro1zing skin and so) 1ssue infec1ons Early surgical consult/ interven3on Empiric an1microbial therapy Piperacillin/tazobactam or carbapenem (group A strep, other gram pos, gram negs and anaerobes) plus Clindamycin (group A strep toxin inhibifon) plus Vancomycin (MRSA) 53 yo M ER physician presents with 9 day history of progressive celluli1s of L forearm. Ini1ally noted a pustule self I&D, started keflex + clindamycin x 4 days. Progressive erythema and drainage. Started IV vanco + ce)riaxone with no improvement a)er 3 days. Case 4 10

Further history History of chronic benign neutropenia 3 weeks ago, trip to Arizona where cleared brush in order to replace a water drip line and scraped his arm 2 weeks ago, worked in home (Merced) vegetable garden clearing eggplant and pepper brushes 7 days ago, cleaned his fish tank No animal or 1ck bites Only recent travel to Arizona All of the following are possible causes of his infec1on EXCEPT: A. Mycobacterium marinum B. Coccidioides immifs C. Nocardia brasiliensis D. Brucella melitensis E. Sporothrix schenkii Gram stain from wound culture Nocardia brasiliensis Nocardia Soil inhabitant Worldwide distribu1on Incuba1on period: <1-6 weeks O)en with mild systemic symptoms Nocardia brasiliensis > asteroides for cutaneous disease Diagnosis: biopsy and culture Par1ally acid- fast, gram variable branching rods. Treatment: TMP- SMX x 4-6 months 11

26 yo M with 6 week history of R hand papule ulcer Mul1ple visits to ED and urgent care, Receives several courses of abx, no improvement Leishmania panamensis Approach to Nodular lymphangi1s Take a good history Obtain biopsy Pathology: stain for fungi and mycobacteria Cultures: bacterial, fungal, and mycobacterial Consider empiric therapy based on severity of disease and history prior to biopsy results Common causes: Sporothrix schenckii, Nocardia, Mycobacterium marinum, Francisella tularensis, Leishmania spp. 12

Which of the following reflect true infec1ous celluli1s? Which of the following reflect true infec1ous celluli1s? True celluli1s Acute on chronic stasis derma11s Acute stasis derma11s Contact derma11s David Derm Online J 2011 Masqueraders of Infec1ous Celluli1s Summary Stasis derma11s Superficial thrombophlebi1s and deep venous thrombosis Contact derma11s Insect s1ngs/1ck bites Drug reac1ons Gouty arthri1s Foreign body reac1on (e.g. surgical mesh, orthopedic implants) Lymphedema Malignancy (e.g. T- cell lymphoma) Falagas ME Ann Intern Med 2005 13

Thank you! catherine.liu@ucsf.edu 14